Molecular dynamics protein hydration

Three theory papers are also included. Determinants of the Polyproline II Helix from Modeling Studies by Creamer and Campbell reexamines and extends an earlier hypothesis about Pn and its determinants. Hydration Theory for Molecular Biophysics by Paulaitis and Pratt discusses the crucial role of water in both folded and unfolded proteins. Unfolded State of Peptides by Daura et al. focuses on the unfolded state of peptides studied primarily by molecular dynamics. 

This bimodal dynamics of hydration water is intriguing. A model based on dynamic equilibrium between quasi-bound and free water molecules on the surface of biomolecules (or self-assembly) predicts that the orientational relaxation at a macromolecular surface should indeed be biexponential, with a fast time component (few ps) nearly equal to that of the free water while the long time component is equal to the inverse of the rate of bound to free transition [4], In order to gain an in depth understanding of hydration dynamics, we have carried out detailed atomistic molecular dynamics (MD) simulation studies of water dynamics at the surface of an anionic micelle of cesium perfluorooctanoate (CsPFO), a cationic micelle of cetyl trimethy-lainmonium bromide (CTAB), and also at the surface of a small protein (enterotoxin) using classical, non-polarizable force fields. In particular we have studied the hydrogen bond lifetime dynamics, rotational and dielectric relaxation, translational diffusion and vibrational dynamics of the surface water molecules. In this article we discuss the water dynamics at the surface of CsPFO and of enterotoxin. 

Molecular dynamics (MD) simulations [29-31], coupled with experimental observations, have played an important role in the understanding of protein hydration. They predicted that the dynamics of ordered water molecules in the surface layer is ultrafast, typically on the picosecond time scales. Most calculated residence times are shorter than experimental measurements reported before, in a range of sub-picosecond to 100 ps. Water molecules at the surface are very mobile and are in constant exchange with bulk water. For example, the trajectory study of myoglobin hydration revealed that among 294 hydration sites, the residence times at 284 sites (96.6% of surface water molecules) are less than lOOps [32]. Furthermore, the population time correlation functions... 

With site-directed mutation and femtosecond-resolved fluorescence methods, we have used tryptophan as an excellent local molecular reporter for studies of a series of ultrafast protein dynamics, which include intraprotein electron transfer [64-68] and energy transfer [61, 69], as well as protein hydration dynamics [70-74]. As an optical probe, all these ultrafast measurements require no potential quenching of excited-state tryptophan by neighboring protein residues or peptide bonds on the picosecond time scale. However, it is known that tryptophan fluorescence is readily quenched by various amino acid residues [75] and peptide bonds [76-78]. Intraprotein electron transfer from excited indole moiety to nearby electrophilic residue(s) was proposed to be the quenching... 

Figure 46. A unified molecular mechanism of protein hydration dynamics and coupled water-protein fluctuations. The initial ultrafast dynamics in a few picoseconds (ii) represents local collective orientation or small translation motions, which mainly depend on local electrostatic interactions. On the longer time (12), the water networks undergo structural rearrangements in the layer, which are strongly coupled with both protein fluctuations and bulk-water dynamic exchange.

Because of the ease with which molecular mechanics calculations may be obtained, there was early recognition that inclusion of solvation effects, particularly for biological molecules associated with water, was essential to describe experimentally observed structures and phenomena [32]. The solvent, usually an aqueous phase, has a fundamental influence on the structure, thermodynamics, and dynamics of proteins at both a global and local level [3/]. Inclusion of solvent effects in a simulation of bovine pancreatic trypsin inhibitor produced a time-averaged structure much more like that observed in high-resolution X-ray studies with smaller atomic amplitudes of vibration and a fewer number of incorrect hydrogen bonds [33], High-resolution proton NMR studies of protein hydration in aqueous... 

Molecular modeling using either Monte-Carlo simulations or molecular dynamics is used to apply molecular mechanics energy minimizations to very complex systems [348]. In complex flexible molecules such as proteins or nucleic adds, the number of variable parameters, i.e., bond torsion angles, is such that the global search for energy minima becomes impossible The same problem occurs with theoretical calculations of water structure in aqueous solutions or in heavily hydrated crystals. 

Hydration is so important for the structural, physical and biological properties of the proteins, that it has been studied by a variety of methods such as Raman, IR and NMR spectroscopy, calorimetry, gravimetry, molecular dynamics [621, 622, 810, 827-834]. 

In the present paper, the method which the authors employed previously to derive an expression for the solubility of various proteins in aqueous solutions, has been extended to the solubility of gases in mixtures of water + strong electrolytes. One parameter equation for the solubility of gases has been derived, which was used to represent the solubilities of oxygen, carbon dioxide and methane in water -i- sodium chloride. In additions, the developed theory could be used to examine the local composition of the solvent around a gas molecule. The results revealed that the oxygen, carbon dioxide and methane molecules are preferentially hydrated in water-i-sodium chloride mixtures. A similar result was obtained for the water -i- methane -i- sodium chloride by molecular dynamics simulations [72]. 

Gu, W. and Schoenborn, B.P. Molecular dynamics simulation of hydration in myoglobin. Proteins Struct. Funct. Genet., 22, 20,1995. 

We also observe a slowing down of the relaxation time T2 related to internal motions. The relaxation time T2 increases from 2.3 ps at ambient pressure to 3.6 ps at 6000 bar. This increase of T2 is accompanied by a slight decrease of the proportion of mobile protons (from 43% at ambient pressure to 39% at 6000 bar) and of the radius of the sphere in which motions occurs (from 3. 6 A at ambient pressure to 3.1 A at 6000 bar). At atmospheric pressure, QENS experiments on other proteins have shown that the motions observed, at similar wave vector and energy transfer ranges, concern protons belonging to the side chains at the surface of the protein . Thus the observed modifications of internal dynamics can only concern lateral chains. Moreover, molecular dynamics simulations have shown that backbone of BPTI is not affected by pressures up to 5000 bar ". A possible explanation about the pressure effects on internal protein motions is that the effect of pressure is to increase the density of first hydration layer at the protein surface. This water density increase induces... 

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